Our long term goal is to improve clinical imaging diagnosis and treatment monitoring for millions of Americans across a broad spectrum of disease. Currently, CT imaging is among the most clinically utilized and valuable tests, particularly for trauma and acute disease, but remains severely limited by 1) its inability to differentiate between the available contrast materials even when modern dual energy CT scanners are utilized; and 2) the potential toxicity of current contrast agents. These limitations result in diagnostic ambiguity when multiple contrast materials are delivered, increased radiation dose lost time and treatment opportunity when separate scans are needed to differentiate injury between different bodily compartments, and denial or delay of contrast delivery for patients at risk for contrast induced nephropathy or reactions. We propose to potentially transform the capability of clinical CT by developing a novel safe non-iodinated injectable contrast agent that can be delivered concurrently with, yet be differentiated from, existing agents to produce high resolution perfectly co-registered Dual Energy CT evaluations of multiple organ systems. We propose to synthesize and test a carefully designed tungsten contrast material with a distinctly different biodistribution and X-ray absorption than those of conventional iodinated agents, allowing these agents to be simultaneously injected, imaged with a clinical Dual Energy CT (DECT) scanner, then quantitatively separated to provide detailed co-registered CT images of vasculature and organ pathology with reduced radiation dose and greater speed than currently possible. The specific aims of our pilot project are to test the following hypotheses 1) The synthesis and desired biophysicochemical characteristics of novel macromolecular tungsten-based contrast materials are highly favorable for the potential use of these agents as injectable CT contrast material. 2) Dual Energy CT quantification of mixed tungsten-based and iodine-based contrast materials is accurate in the relevant clinical range of contrast concentrations in vitro. 3) Dual contrast material-enhanced DECT is feasible in vivo. Our research collaboration brings together a uniquely qualified team of a CT radiologist with experience in dual energy CT and novel contrast material development, contrast material chemists with expertise and experience in macromolecular contrast material development, medical imaging physicists (R1-1), computer programmers (R1-4, R2-2) and consultant experts in organometallic tungsten chemistry to synthesize and test our proposed novel class of contrast material. Development of a tungsten-based CT contrast material would quickly open doors to markedly improved speed and safety in imaging diagnosis, surgical planning and treatment monitoring for a wide spectrum of human disease. We designed our aims rationally so that the success of each will remove obstacles for the development of valuable novel contrast agents for dual energy CT, and the success of each aim is independent from the outcome of either of the other two. PUBLIC HEALTH RELEVANCE: Although contrast-enhanced CT imaging is widely used and valued for its ability to rapidly provide three dimensional images of internal organs and vasculature, these scans are limited by their inability, even with modern equipment, to tell which contrast material is in which body part, and by concerns for the safety of available contrast agents. We propose to synthesize and test a novel class of tungsten-based macromolecules that is carefully designed to complement the X-ray spectra absorption and biodistribution of current iodinated agents to allow simultaneous injection of both agents and allow modern dual energy CT scanners to readily tell which bodily compartment is enhanced with which agent. Availability of dual contrast enhanced dual energy CT scanning should rapidly open doors to improve the speed, safety, and accuracy of imaging diagnosis, surgical planning and treatment monitoring for a wide spectrum of human disease in millions of Americans.